Abstract
Protein kinase C (PKC) has been shown to regulate the ethanol sensitivity of membrane-bound receptors and transporters, but little is known about the molecular mechanisms underlying this regulation. PKC is a family of isozymes that translocate to new intracellular sites on activation. Here we present immunochemical data showing that ethanol causes translocation of δ- and ε-PKC to new intracellular sites. Ethanol causes translocation of δ-PKC from the Golgi to the perinucleus; this translocation is similar to that induced by activation of PKC with phorbol esters. In contrast, ε-PKC translocation caused by ethanol is different from that induced by phorbol esters; ethanol causes translocation of ε-PKC from the perinucleus to the cytoplasm, whereas phorbol ester activation causes translocation of ε-PKC to the nucleus. Because the substrate specificity of these kinases is determined by their site of localization, ethanol-induced translocation of δ- and ε-PKC to new intracellular sites may explain some of the pleiotropic effects of ethanol on cellular functions.
Footnotes
- Received June 10, 1997.
- Accepted July 10, 1997.
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Send reprint requests to: Adrienne S. Gordon, Ph.D., Ernest Gallo Clinic and Research Center, San Francisco General Hospital, 1001 Potrero Avenue, Building 1, #101, San Francisco, CA 94110-3518. E-mail:adrienn{at}itsa.ucsf.edu
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↵1 Current affiliation: Exelixis Pharmaceuticals, Oakland, CA 94606.
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↵2 Current affiliation: Department of Biology, York University, North York, Ontario M3J 1P3, Canada.
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This work was supported in part by National Institutes of Health Grant AA10039.
- The American Society for Pharmacology and Experimental Therapeutics
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